DESCRIPTION (Applicant's abstract): There have been a growing number of reports associating schizophrenia with lateralized pathology in the brain, in most cases implicating dysfunction in the left hemisphere. Studies reporting hemispheric asymmetries in schizophrenia have utilized diverse methodologies, including magnetic resonance imaging, positron emission tomography, neuropathology and chemopathology, motor assessments, event-related potentials, and neuropsychological assessments. There is a smaller body of literature regarding lateralized pathology in bipolar disorder, which suggests that there may be greater right than left hemisphere involvement in this condition. Because findings related to hemispheric asymmetry are among the most commonly reported psychobiological findings in schizophrenia with localizing value, we considered that laterality assessments may be associated with psychopathological symptoms and illness outcome (quality of life) as well. Further, because some investigators have theorized that schizophrenia and bipolar illness may in fact be closely related, we considered that measures of laterality may also shed light on the relationship of these two conditions, with schizophrenia being associated with greater left hemisphere impairment, and bipolar disorder with greater right hemisphere impairment. We have recently completed studies of upper extremity motor instability which support this idea. In the current proposal we plan to assess patients with schizophrenia, bipolar disorder, and healthy comparison subjects to determine if these groups differ from each other on measures of lateralized function over a six month interval. Measures include L and R motor, sensory, and cognitive function (hand force instability and rigidity, dichotic listening, Warrington Recognition Memory Test Posner Test, verbal and figural fluency Consonant-Vowel-Consonant Test, Chair Identification Test), and brain function (functional MRI). We also plan to determine if these same measures relate to the positive psychotic symptoms, manic symptoms, and illness outcome as reflected in a measure of quality of life (Quality of Well Being Scale). The longitudinal nature of the study allows us to address important trait and state issues. We hope these studies will provide insights into the localization of pathology in schizophrenia and bipolar disorder, as well as their relationship to each other.